Periodontal diseases are infectious diseases caused by the microorganisms that exist at or below the gingival margin. As such, the optimum method for their control logically lies in the elimination or suppression of the etiologic species. Thus, the long-term objective of this Program Project grant is to control periodontal infections by suppressing or eliminating the organisms that cause them. Barriers to this process have included uncertainty in defining specific etiologic gents, lack of order in our understanding of the complex ecosystem that colonizes the periodontal structures, difficulty in enumerating a wide range of taxa in the very large numbers of samples required to perform treatment, prevention or ecology studies and lack of effective therapeutic modalities even if the agent(s) were known. These barriers have in part been overcome. Means to assemble and analyze large scale data bases describing intraoral prevalence and numbers of organisms have provided new insight and a degree of order in describing the sub- gingival ecosystem. Complexes of associated microbial species appear to form a succession in plaque development. One complex, determined the "red complex," consisting of Bacteroides forsythus, Porphyromonas gingivalis and Treponema denticola appears to be a major etiologic contributor to the common adult forms of periodontitis and thus a prime target for anti-microbial strategies. Parallel to the advances in understanding oral ecology, new laboratory methods have been introduced. Studies of the efficacy of antimicrobial approaches become feasible due to the efficiency of techniques such and checkerboard DNA-DNA hybridization. Improved methods for control of periodontal infections have also been developed. These include effective antibacterial dentifrices and mouthwashes, powered toothbrushes, local drug delivery systems and better systemic antimicrobial therapies. The Projects in this application will take advantage of these developments. ore will provide services central to all Projects including administration, clinical recruitment and monitoring, checkerboard hybridization and biostatistics. Methods for the targeted elimination of the red complex will be evaluated in Project 1 (prevention) and B (treatment). Adverse effects arising from these procedures in terms of emergence of undesired or antibiotic resistant species will be evaluated in Project C. Project D will examine the ecological relationships of oral species and their habitat.